Significance Human granulocytic ehrlichiosis (HGE) is an emerging rickettsial infectionaffecting humans and possibly horses, dogs, other companion animals and wildlife species. The HGE agent is either identical to, or very closely related to Ehrlichia equi, a cause of significant morbidity in horses and dogs. A nonhuman primate model of HGE would facilitate studies of diagnosis, pathogenesis, therapeutic management, and prevention. Objectives The objectives of this study were to evaluate a potential rhesus macaque model of HGE and determine the clinical course and pathogenesis following inoculation with an HGE agent isolate derived from a fatal human case. Results Two adult rhesus macaques inoculated IV with HGE-agent exhibited pyrexia and lethargy days 4-12 pi. Hematological abnormalities included transient neutropenia, thrombocytopenia, and mild anemia. Ehrlichial morulae were present in monocytes and neutrophils on days 4-12 pi, and detection of HGE DNA in peripheral blood was positive by PCR over this time period. Bone marrow samples were PCR positive on day 11 pi. Seroconversion was complete by day 20 pi, at a titer of 1:100. Seroconversion coincided with clinical recovery and clearance of HGE from peripheral blood. Future Directions This pilot study has demonstrated the feasibility and potential utility of a macaque model of HGE. This model will be further utilized to develop improved methods of diagnosis, and to investigate HGE pathogenesis, therapy, and prevention. KEYWORDS ehrlichiosis, rickets